The broad objective of this proposal is to compare the pharmacological, physiological and biochemical status of vascular smooth muscle from normotensive and hypertensive animals (rat, rabbit, dog). This will be carried out through a cooperative effort on the part of the 4 participating laboratories (in 2 departments). Vascular smooth muscle from normotensive and hypertensive animals will be compared with respect to: a) Their reactivity to various endogenous spasmogens (e.g. angiotensin II, norepinephrine, K ion, etc.) and vasodilators (e.g. adenosine). The possibility that increases in vascular reactivity is equivalent to the well known phenomena of smooth muscle supersensitivity will also be evaluated. Precise measurements of force per cross-sectional area (i.e., Newtons/m squared) will be used to minimize artifacts due to the well known changes in the vessel wall seen in chronic hypertensive states. A careful time course (including reversal) will also be carried out to attempt to correlate changes with the development or remission of hypertension. b) The utilization, compartmentalization and biochemical handling of Ca ions. This will include evaluation of electromechanical and pharmacomechanical utilization of intracellular and extracellular Ca ion's pools, uptake and release of Ca ions from isolated sarcoplasmic reticulum and Ca ions requirements for purified actomyosin ATPase. Phosphorylation of myosin in isolated proteins and intact strips will also be evaluated. c) The relationship of cell energetics to contractile activity. This will include studies on O2 sensitivity of normotensive and hypertensive smooth muscle. Also relation of energy metabolism (e.g., ATP, ADP, AMP, adenosine, lactic acid, etc.) to vascular reactivity. d) Mechanical studies to determine if the physical and geometric properties of the vasculature or the smooth muscle cells are altered in the hypertensive state. These will include study of the length-tension relationship, uniformity of response, contribution of passive tension to wall tension and relationship of mean cell length to muscle length.